Andrew R Chapman1, Kuan Ken Lee1, David A McAllister2, Louise Cullen3,4,5, Jaimi H Greenslade3,4,5, William Parsonage3,4,5, Andrew Worster6, Peter A Kavsak7, Stefan Blankenberg8, Johannes Neumann8, Nils A Sörensen8, Dirk Westermann8, Madelon M Buijs9, Gerard J E Verdel10, John W Pickering11,12, Martin P Than12, Raphael Twerenbold13, Patrick Badertscher13, Zaid Sabti13, Christian Mueller13, Atul Anand1, Philip Adamson1, Fiona E Strachan1, Amy Ferry1, Dennis Sandeman1, Alasdair Gray1,14, Richard Body15, Brian Keevil16, Edward Carlton17, Kim Greaves18, Frederick K Korley19, Thomas S Metkus20, Yader Sandoval21, Fred S Apple22, David E Newby1, Anoop S V Shah1, Nicholas L Mills1. 1. BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland. 2. Institute of Health and Wellbeing, University of Glasgow, Glasgow, Scotland. 3. Department of Emergency Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia. 4. School of Medicine, University of Queensland, Brisbane, Australia. 5. Faculty of Health, Queensland University of Technology, Brisbane, Australia. 6. Division of Emergency Medicine, McMaster University, Hamilton, Ontario, Canada. 7. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. 8. University Heart Center, Hamburg, Germany. 9. Atalmedial Diagnostic Centers, Hoofddorp, the Netherlands. 10. Department of Cardiology, Spaarne Gasthuis, Haarlem, the Netherlands. 11. Department of Medicine, University of Otago, Christchurch, New Zealand. 12. Emergency Department, Christchurch Hospital, Christchurch, New Zealand. 13. Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital, Basel, Switzerland. 14. Department of Emergency Medicine and EMERGE, Royal Infirmary of Edinburgh, Edinburgh, Scotland. 15. Central Manchester University Hospitals NHS Foundation Trust and the University of Manchester, Manchester, England. 16. University Hospital South Manchester NHS Foundation Trust, Manchester, England. 17. Department of Emergency Medicine, Southmead Hospital, Bristol, England. 18. Department of Cardiology, Sunshine Coast University Hospital, University of the Sunshine Coast, Birtinya, Australia. 19. University of Michigan Medical School, Ann Arbor. 20. John Hopkins School of Medicine, Baltimore, Maryland. 21. Hennepin County Medical Center and Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota. 22. Department of Laboratory Medicine and Pathology, Hennepin County Medical Center and University of Minnesota, Minneapolis.
Abstract
Importance: High-sensitivity cardiac troponin I testing is widely used to evaluate patients with suspected acute coronary syndrome. A cardiac troponin concentration of less than 5 ng/L identifies patients at presentation as low risk, but the optimal threshold is uncertain. Objective: To evaluate the performance of a cardiac troponin I threshold of 5 ng/L at presentation as a risk stratification tool in patients with suspected acute coronary syndrome. Data Sources: Systematic search of MEDLINE, EMBASE, Cochrane, and Web of Science databases from January 1, 2006, to March 18, 2017. Study Selection: Prospective studies measuring high-sensitivity cardiac troponin I concentrations in patients with suspected acute coronary syndrome in which the diagnosis was adjudicated according to the universal definition of myocardial infarction. Data Extraction and Synthesis: The systematic review identified 19 cohorts. Individual patient-level data were obtained from the corresponding authors of 17 cohorts, with aggregate data from 2 cohorts. Meta-estimates for primary and secondary outcomes were derived using a binomial-normal random-effects model. Main Outcomes and Measures: The primary outcome was myocardial infarction or cardiac death at 30 days. Performance was evaluated in subgroups and across a range of troponin concentrations (2-16 ng/L) using individual patient data. Results: Of 11 845 articles identified, 104 underwent full-text review, and 19 cohorts from 9 countries were included. Among 22 457 patients included in the meta-analysis (mean age, 62 [SD, 15.5] years; n = 9329 women [41.5%]), the primary outcome occurred in 2786 (12.4%). Cardiac troponin I concentrations were less than 5 ng/L at presentation in 11 012 patients (49%), in whom there were 60 missed index or 30-day events (59 index myocardial infarctions, 1 myocardial infarction at 30 days, and no cardiac deaths at 30 days). This resulted in a negative predictive value of 99.5% (95% CI, 99.3%-99.6%) for the primary outcome. There were no cardiac deaths at 30 days and 7 (0.1%) at 1 year, with a negative predictive value of 99.9% (95% CI, 99.7%-99.9%) for cardiac death. Conclusions and Relevance: Among patients with suspected acute coronary syndrome, a high-sensitivity cardiac troponin I concentration of less than 5 ng/L identified those at low risk of myocardial infarction or cardiac death within 30 days. Further research is needed to understand the clinical utility and cost-effectiveness of this approach to risk stratification.
Importance: High-sensitivity cardiac troponin I testing is widely used to evaluate patients with suspected acute coronary syndrome. A cardiac troponin concentration of less than 5 ng/L identifies patients at presentation as low risk, but the optimal threshold is uncertain. Objective: To evaluate the performance of a cardiac troponin I threshold of 5 ng/L at presentation as a risk stratification tool in patients with suspected acute coronary syndrome. Data Sources: Systematic search of MEDLINE, EMBASE, Cochrane, and Web of Science databases from January 1, 2006, to March 18, 2017. Study Selection: Prospective studies measuring high-sensitivity cardiac troponin I concentrations in patients with suspected acute coronary syndrome in which the diagnosis was adjudicated according to the universal definition of myocardial infarction. Data Extraction and Synthesis: The systematic review identified 19 cohorts. Individual patient-level data were obtained from the corresponding authors of 17 cohorts, with aggregate data from 2 cohorts. Meta-estimates for primary and secondary outcomes were derived using a binomial-normal random-effects model. Main Outcomes and Measures: The primary outcome was myocardial infarction or cardiac death at 30 days. Performance was evaluated in subgroups and across a range of troponin concentrations (2-16 ng/L) using individual patient data. Results: Of 11 845 articles identified, 104 underwent full-text review, and 19 cohorts from 9 countries were included. Among 22 457 patients included in the meta-analysis (mean age, 62 [SD, 15.5] years; n = 9329 women [41.5%]), the primary outcome occurred in 2786 (12.4%). Cardiac troponin I concentrations were less than 5 ng/L at presentation in 11 012 patients (49%), in whom there were 60 missed index or 30-day events (59 index myocardial infarctions, 1 myocardial infarction at 30 days, and no cardiac deaths at 30 days). This resulted in a negative predictive value of 99.5% (95% CI, 99.3%-99.6%) for the primary outcome. There were no cardiac deaths at 30 days and 7 (0.1%) at 1 year, with a negative predictive value of 99.9% (95% CI, 99.7%-99.9%) for cardiac death. Conclusions and Relevance: Among patients with suspected acute coronary syndrome, a high-sensitivity cardiac troponin I concentration of less than 5 ng/L identified those at low risk of myocardial infarction or cardiac death within 30 days. Further research is needed to understand the clinical utility and cost-effectiveness of this approach to risk stratification.
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